Antidepressant Withdrawal, Online Data, and a Bottom Line

A recent article in the New York Times¹ and another in the current print edition of Psychiatric Times² express concern about antidepressant withdrawal syndrome. These articles raise the question: how many people who begin taking an antidepressant will have severe difficulties when they try to taper off?

Surprisingly, this has not been directly studied (per an hour’s negative search on PUB MED, consistent with work by a UCLA social psychologist³). Indirectdata suggest the answer is "a lot."^4,5 Several clinical trials underway will generate relevant data^{(eg, 6,7)} but they are still not designed specifically to answer this crucial question.

For further insight, we can look at online communities referenced in the PT article. One of the most advanced of these is SurvivingAntidepressants.org. If testimonials might sway your opinion about the potential severity of antidepressant withdrawal difficulties, this site has hundreds.

Testimonials are easy to dismiss. But regardless of your opinion of testimonials as evidence, the posts at SurvivingAntidepressants.org make one thing clear: venlafaxine is among the most difficult of the antidepressants to discontinue. The large steps between dosage strengths require alternative intermediate strategies, but the large number of beads in each capsule make subdivision difficult (one member describes using a grass seed counter to count individual beads). See the Box for a representative post and notice that the author “is capable of differentiating their [sic] own symptoms," eg, insomnia, from withdrawal symptoms.

Other reasons

We have other reasons to avoid venlafaxine. Unlike SRIs, it can raise blood pressure, worsening hypertension, an all-too-common comorbidity with depression. Venlafaxine has also been found more likely to cause manic symptoms, in patients with bipolar disorder, than other antidepressant such as sertraline and bupropion.⁸ Since ruling out bipolarity is difficult, and since we have many alternatives to venlafaxine with just as much evidence for their efficacy, one can simply choose something else.

Paroxetine causes significantly more weight gain than other SRIs,⁹ so skip over that one too. Interestingly, paroxetine also appears disproportionately among patients searching for information about how to stop antidepressants.¹⁰

Citalopram can cause arrhythmias in patients with long QT syndrome¹¹ so rather than putting patients through the hassle of serial electrocardiograms, skip over that one too.

Alternative antidepressants

This leaves fluoxetine, sertraline-and bupropion. According to a meta-analysis I reviewed in 2016,¹² bupropion is nearly as effective for anxiety as are SRIs, counter to general beliefs. And compared with venlafaxine, it has a far lower propensity to induce manic symptoms.⁸

As published case reports^13,14 and SurvivingAntidepressants.org posts show, stopping bupropion can cause withdrawal symptoms too. But on that website, the density of posts about bupropion is far lower than for venlafaxine (143 versus 2130-among posts numbering over 300,000), which certainly matches my clinical experience of difficulties with bupropion discontinuation: far fewer than with all other antidepressants.

Conclusion

Before starting any antidepressant, share with the patient the potential for difficult withdrawal when stopping it. This is tricky-because we don’t know how often people have horrendous experiences that are truly a result of the discontinuation. The folks at SurvivingAntidepressants.org think that we who prescribe antidepressants grossly underestimate the latent risk they carry. At minimum, they would tell us loudly: stop starting venlafaxine.

References:

1. Carey B. Gebeloff R. Many People Taking Antidepressants Discover They Cannot Quit. The New York Times. April 7, 2018. https://www.nytimes.com/2018/04/07/health/antidepressants-withdrawal-prozac-cymbalta.html. Accessed May 1, 2018.

2. Witt-Doering J, Shorter D, Kosten T. Online communities for drug withdrawal: what can we learn?Psychiatric Times. 2018;35:1-4, 14.

3. Cohen D, quoted in Rahhal N. Tens of millions of Americans are struggling to get off antidepressants-and going to extreme lengths to quit. Daily Mail.com, April 9 2018.

4. Ostrow L, Jessell L, Hurd M, et al. Discontinuing Psychiatric Medications: A Survey of Long-Term Users. Psychiatr Serv. 2017;68:1232-1238.

5. Cartwright C, Gibson K, Read J, et al. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Prefer Adherence. 2016;10:1401-1407.

6. US National Library of Medicine. ClinicalTrials.gov. Tapering Off Antidepressants. NCT02661828.

7. US National Library of Medicine. ClinicalTrials.gov. Discontinuation of Antidepressant Medication in Primary Care. NCT03361514.

8. Post RM, Altshuler LL, Leverich GS, et al. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006;189:124-131.

9. Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71:1259-1272.

10. Abbe A, Falissard B. Stopping Antidepressants and Anxiolytics as Major Concerns Reported in Online Health Communities: A Text Mining Approach. JMIR Ment Health. 2017;4:e48.

11. Wang M, Szepietowska B, Polonsky B, et al. Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With Long QT Syndrome. Am J Cardiol. 2018;121:182-187.

12. Phelps J. Is Bupropion Your No. 1 Antidepressant Choice? Psychiatric Times. June 6, 2016. http://www.psychiatrictimes.com/bipolar-disorder/bupropion-your-no-1-antidepressant-choice. Accessed May 1, 2018.

13. Berigan TR, Harazin JS. Bupropion-Associated Withdrawal Symptoms: A Case Report. Prim Care Companion. J Clin Psychiatry. 1999;1:50–51.

14. Berigan TR. Bupropion-Associated Withdrawal Symptoms Revisited: A Case Report. Prim Care Companion J Clin Psychiatry. 2002;4:78.